Outline

Objective

To assess the risk for hypothalamo-pituitary dysfunction associated with Linear accelerator (LINAC) based radiosurgery (RS) of pituitary macroadenomas.

Methods

From August 1990 through December 2003, 177 patients with pituitary macroadenoma were treated with LINAC-RS according to a prospective protocol, which prescribed the maximum therapeutic radiation dose to be 20 Gy. Until 1996, treatment planning based solely on computed-tomography (CT)-imaging. Since 1997, magnetic-resonance-imaging (MRI) has been routinely integrated. Patients with a minimum actualized follow-up of 12 months, no radiation exposure and no deficit of pituitary function prior to LINAC-RS were considered for evaluation of the “real” risk analyzing multiple variables in a Cox-regression model.

Results

58 patients (median age: 50.5 yrs) with either nonfunctioning (n=11) or hormone-secreting pituitary macroadenoma (median tumour volume: 2.2 cc) were at risk. The median actualized follow-up time was 53.7 mth (range: 16.2-112 mth). A median single dose of 16.5 Gy (range 10-20 Gy) gained local tumour control in >90% of the cases. Normalization of endocrinopathology was documented in 57.7% of the patients with hormone active adenomas. Within a median time of 43.4 mth, 8/58 pts. (13.8%) presented with new insufficiency of anterior pituitary function. None of the variables treatment planning imaging (CT vs. CT/MRI), surgery prior to LINAC-RS, number of surgical interventions, volume of pituitary exposed to different doses (5-20Gy), maximum radiation dose delivered to the pituitary/hypothalamic region (median: 19.2 Gy, range: 5-46 Gy), diabetes mellitus, and nicotine abuse were significantly associated with radiation-induced pituitary damage. Only the presence of “arterial hypertension” significantly increased the risk for pituitary dysfunction (p=0,028).

Conclusions

LINAC-RS using round collimators and a reduced therapeutic dose was highly effective for local tumour control and normalization of hormone hypersecretion. In this protocol, not the applied radiation dose but a risk factor, which alters vessels in general, hence probably modifying the radiation tolerance of small vessels, determined significantly the occurrence of radiation-induced pituitary dysfunction.